Bacterial infections and similar diseases are a common problem related to growth and transfer of microbes in the use of many types of medical devices.
For example, indwelling medical devices such as vascular catheters, peritoneal catheters, cardiovascular devices, orthopedic implants and other prosthetic devices is often offset by infectious complications. The most common organisms causing these infectious complications are Staphylococcus epidermidis and Staphylococcus aureus. In the case of vascular catheters, these two organisms account for almost 70-80% of all infectious organisms, with Staphylococcus epidermidis being the most common organism. Candida albicans, a fungal agent, accounts for about 10-15% of catheter infections.
Another common hospital-acquired infection is urinary tract infection (UTI). The majority of cases of UTI are associated with the use of urinary catheters, including hydrophilic catheters with hydrophilic coatings for intermittent use. Each catheter is normally pre-packed in a receptacle by the manufacturer, in order to maintain the catheter in a clean and preferably sterile condition. These urinary catheters are inserted in a variety of populations, including the elderly, stroke victims, spinal cord-injured patients, post-operative patients and those with obstructive uropathy. Despite adherence to sterile guidelines for the insertion and maintenance of urinary catheters, catheter-associated UTI continues to pose a major problem. For instance, it is estimated that almost one-quarter of hospitalized spinal cord-injured patients develop symptomatic UTI during their hospital course. Gram-negative bacilli account for almost 60-70%, enterococci for about 25% and Candida species for about 10% of cases of UTI. When medical devices such as a catheter with a hydrophilic coating is introduced into the human cavity, the normal human defense barrier may be penetrated which can result in introduction of bacteria, fungi, vira, or tissue-like or multiple organized cells. It is well known that persons practicing intermittent urethral catheterization as a daily routine often have problems with symptomatic UTI. Similarly, a number of other medical devices that come in intimate contact with human tissue can cause microbial infections.
Colonization of bacteria on the surfaces of the catheter or other part of the device can produce serious patient problems, including the need to remove and/or replace the implanted device and to vigorously treat secondary infective conditions. A considerable amount of attention and study has been directed toward preventing such colonization by the use of antimicrobial agents, such as antibiotics, bound to the surface of the materials employed in such devices. In such attempts the objective has been to produce a sufficient bacteriostatic or bactericidal action to prevent colonization. For example, methods of coating surfaces of medical devices with antibiotics are taught in U.S. Pat. No. 4,895,566 (a medical device substrate carrying a negatively charged group having a pKa of less than 6 and a cationic antibiotic bound to the negatively charged group); U.S. Pat. No. 4,917,686 (antibiotics are dissolved in a swelling agent which is absorbed into the matrix of the surface material of the medical device); U.S. Pat. No. 4,107,121 (constructing the medical device with ionogenic hydrogels, which thereafter absorb or ionically bind antibiotics); U.S. Pat. No. 5,013,306 (laminating an antibiotic to a polymeric surface layer of a medical device); and U.S. Pat. No. 4,952,419 (applying a film of silicone oil to the surface of an implant and then contacting the silicone film bearing surface with antibiotic powders). U.S. Pat. No. 4,612,337 discloses an implantable medical device comprising a non-metallic material, and an antimicrobial composition, of an effective concentration to inhibit the growth of bacterial and fungal organisms, coating the surface of the implant and impregnating the non-metallic material of the medical implant.
It is also known to use antimicrobial compounds without antibiotic effects. For example, it is known from EP 1 104 311 to use silver as an antibacterial agent, and it is known from WO 2004/075944 to use hydrogen peroxide to the same end.
However, a problem related to many of the prior art solutions are that they are relatively costly and complex to produce. A further problem is the many negative secondary effects associated with most of the proposed anti-microbial compounds.
There is therefore a need for an antimicrobial compound and coating that can provide high bactericidal efficacy and broad spectrum antimicrobial activity coupled with low cytotoxicity. There is also a need for a cost effective product.